背景：食管鳞癌(ESCC)是一种常见的侵袭性强且死亡率高的恶性肿瘤，其5年总生存率不足20％。由于其发生、发展机制复杂，目前尚未找到有效的分子靶点和预后分子标志物。在食管鳞癌进程中，共激活因子激活物CoAA(Coactivator activator)，作为一种独特的转录共调节因子起到促癌功能。CoAA具有的RRMs结构和YQ结构域促使其具有转录激活和调控选择性剪接的功能，从而参与各种癌症相关的生物学过程。 实验设计：在体外细胞实验中，采用PCR的方法检测食管鳞癌细胞系和永生化细胞系中CoAA的mRNA水平；利用MTT实验和transwell迁移、侵袭实验比较转染siRNA-CoAA组和对照组的细胞的存活、迁移和侵袭能力的变化。同时，建立稳定转染CoAA的过表达食管鳞癌细胞系，研究CoAA过表达对食管鳞癌细胞存活、增殖、迁移和侵袭能力的影响，并通过软琼脂集落形成实验和裸鼠异种移植瘤研究CoAA对食管鳞癌细胞成瘤能力的影响。通过CoAA过表达细胞和对照细胞的表达谱芯片检测数据进一步分析CoAA在食管鳞癌中的生物学功能和参与调控的分子信号通路。 结果：体外细胞实验结果显示，CoAA在食管鳞癌细胞系中广泛高表达。siRNA干扰CoAA表达后，食管鳞癌细胞的活力以及迁移和侵袭能力显著降低，其中迁移和侵袭能力分别仅为对照组的48.4％和5.24％；而稳定转染过表达CoAA进一步显著增强了上述的细胞恶性特征，同时促进了细胞的增殖和锚定非依赖性生长能力。体内裸鼠异种移植瘤实验显示，与HKESC-3-vector细胞相比，过表达CoAA显著地促进HKESC-3细胞的成瘤率(71.4％vs 100％)。同时，CoAA过表达细胞移植瘤的生长能力显著增强，其成瘤体积大小是对照细胞成瘤体积的4.08倍。基因表达谱芯片结果显示CoAA过表达导致大量癌症相关基因异常表达，达到2019个基因，从而影响了多种病理生理过程，包括细胞生长和增殖，细胞运动，细胞间相互作用和信号传递，细胞发育等。CoAA过表达也促进了癌症相关信号通路的异常激活，主要包括WNT信号通路和ECM-受体相互作用信号通路。 结论：CoAA促进食管鳞癌细胞存活、增殖，迁移和侵袭能力。CoAA参与了各种病理进程并导致了多种癌症相关信号通路的异常活化。说明CoAA作为一种共激活子激活物，可能在调控食管鳞癌发生和发展进程的网络处于“中心枢纽”位置，具有作为食管鳞癌独立预后因子以及新的治疗靶点的潜能。 关键词：CoAA，细胞增殖，迁移和侵袭，食管鳞癌，分子机理

 Background: Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. Yet the effective prognostic markers and therapeutic targets are not identified. CoAA, containing two RRM-binding region and YQ domain, can stimulate transcriptional activation and regulate alternative splicing, leading to various cancer related biological progression. Here, we characterized the oncogenic roles of Coactivator Activator (CoAA), a unique transcriptional coregulator, in human ESCC progression. Experimental Design: CoAA mRNA level in ESCC cell lines and immortalized esophageal epithelium cell lines were detected by PCR. MTT assay and transwell migration/invasion assay were performed to study cell viability, cell migratory and invasive ability in CoAA knockdown cells and CoAA overexpression cells. We also detected the cell growth ability of CoAA overexpression cells by soft agar assay in vitro and xenograft in nude mice. Furthermore, to confirm CoAA biological function and identify genetic pathways in CoAA overexpression cells, we preformed genome-wide transcript expression profiling using Agilent oligonucleotide arrays. Results: CoAA was overexpressed in ESCC cell lines. Silencing CoAA by specific interference RNA decreased cell viability, migration and invasive activity of ESCC cells, while CoAA overexpression rendered tumor cells to more abilities of aforementioned malignant properties and facilitated the anchorage-independent growth. Xenograft with CoAA overexpression exhibited remarkably increased 4.08 fold tumorigenic ability in nude mice. Further, genome-wide transcript expression profiling revealed that CoAA overexpression resulted in aberrant activation of a broad range of cancer-related genes (2019 genes). And CoAA trigger multiple pathological processes, including cell growth and proliferation, cellular movement, cell-to-cell signaling and interaction, cell death and survival. Meanwhile, CoAA overexpression also activated diverse cancer-related pathways, such as WNT signaling pathway, ECM receptor interaction signal pathway. Conclusion: CoAA promotes cell viability, proliferation, migration and invasion of ESCC cells. Dysregulated CoAA involved in diverse pathological processes and then integrates multiple signal pathways in ESCC cells. All above results suggested that CoAA, a coactivator activator, plays a crucial role in the regulation of ESCC progression. And CoAA will be as a promising prognostic and therapeutic target for ESCC. Keywords: CoAA, cell proliferation, migration and invasion, ESCC, molecular mechanism